A bibliometric analysis of research trends and global perspectives on lung large cell neuroendocrine cancer

Introduction

Lung cancer represents a significant global public health challenge, being the most prevalent malignant tumor with an incidence rate accounting for 11.4% of all cancer cases worldwide. Additionally, it holds the highest rank in cancer-related mortality (1). Studies show that the disease burden and medical costs of lung cancer are rising each year (2,3). Nevertheless, the absence of specific early clinical symptoms often results in patients presenting with advanced stages of the disease upon the onset of symptoms (4). Lung large cell neuroendocrine carcinoma (LCNEC) is a rare subtype of lung cancer, representing 1–3% of cases (5). Despite its rarity, the large number of global lung cancer cases means 22,000 to 66,000 new LCNEC cases are diagnosed annually, surpassing most rare diseases (6). LCNEC is characterized by its aggressive nature, frequently presenting at advanced stages with distant metastases (7,8). The absence of well-defined diagnostic and treatment protocols can be attributed to its unique histological and immunophenotypic features.

LCNEC is recognized as a notably aggressive and heterogeneous subtype of lung cancer, has conventionally been treated using therapeutic protocols adapted from small cell lung cancer (SCLC) management. Despite these efforts, clinical outcomes have remained suboptimal. Therefore, a thorough comprehension of current research on lung adenocarcinoma treatments is essential. This understanding can facilitate the identification of promising therapeutic strategies, elucidate prevailing research trends, pinpoint existing knowledge gaps, and suggest potential new directions for future research endeavors.

Bibliometrics is a prevalent scientometric approach employed to quantitatively evaluate various levels of academic activity, encompassing individual researchers, institutional bodies, and national research systems. It offers a systematic assessment of scholarly productivity and impact (9-11). Furthermore, bibliometrics facilitates the calculation and analysis of publication patterns, enabling a rigorous examination of disciplinary development, the identification of emerging frontier areas, and the detection of knowledge gaps (12). Our investigation represents the inaugural bibliometric analysis of literature pertaining to LCNEC. Utilizing bibliometric methodologies, our team conducted a comprehensive and systematic evaluation of the extant research on LCNEC. The primary objective is to furnish clinicians with an in-depth understanding of the current status, recent advancements, and emerging trends within the domain of LCNEC research. These insights are intended to inform future research endeavors, thereby promoting more profound and clinically significant studies. We present this article in accordance with the BIBLIO reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-727/rc).

Methods

Data sources and retrieval strategies

This paper chooses the Web of Science Core Collection (WoSCC) for its high-quality resources, wide disciplinary scope, and benefits like literature tracing and citation tracking (13). The WoSCC offers numerous high-quality journal articles and detailed citation data, making it a popular tool for bibliometric studies in medicine (14,15). Following extensive deliberations within our research team and consultations with senior experts in literature retrieval, we executed a comprehensive search of the Science Citation Index Expanded (SCI-EXPANDED) within the Web of Science Core Collection. The search strategy employed the following terms: TS=(“Large Cell Neuroendocrine Carcinoma” OR “LCNEC” OR “Pulmonary Large Cell Neuroendocrine Carcinoma”) AND TS=(lung OR pulmonary OR “lung cancer” OR “lung neoplasm”)) NOT TS=(“Small Cell Lung Carcinoma” OR “Carcinoid Tumor” OR “Atypical Carcinoid Tumor”). The inclusion criteria for this study were defined as follows: (I) publication date ranging from January 1, 2000, to December 31, 2024; (II) document type restricted to “article” or “review.” The exclusion criteria encompassed: (I) editorials, letters, news articles, conference papers, and other non-research documents; (II) duplicate articles; (III) articles deemed irrelevant to the research topic upon thorough review.

On March 20, 2025, two independent authors conducted database searches and participated in the full screening process. An experienced corresponding author resolved any disputes. A total of 694 articles on lung large cell neuroendocrine carcinoma were included, as detailed in Figure 1. The literature was exported in plain text format as “Full Record and Cited Reference”.

Figure 1 Flow chart of the process of screening LCNEC literature. LCNEC, large cell neuroendocrine carcinoma.

Statistical analysis

The study utilized R software version 4.4.3 and RStudio to apply bibliometric methods, creating a global literature distribution network on “large cell neuroendocrine carcinoma of the lung”. It involved data mining and analysis of journals, authors, citations, keywords, institutions, countries, and co-occurrence networks. Data with “Full Record and Cited References” from the Web of Science Core Collection was exported as “Plain text file”. The “Bibliometrix” package analyzed various metrics, including article distribution over time, document type and quantity, average publication year and citations, author statistics, most prolific authors and cited works, corresponding author countries, publication counts, total country citations, key sources and keywords, collaboration networks, and thematic maps (16). In addition, we also applied Citespace 5.8 R5 to visualize the research trends of scientific literature.

Results

Obtaining relevant literature

A search on “pulmonary large cell neuroendocrine carcinoma” from January 1, 2000, to December 31, 2024, found 694 relevant articles from 48 countries, 1,084 institutions, and 4,312 authors. These articles averaged 30 citations each, totaling 21,228 citations.

Annual publications and citation trend analysis

The bibliometric analysis of literature pertaining to LCNEC indicates a marked upward trajectory in the annual number of publications within this domain from 2000 to 2024 (Figure 2). During the period from 2000 to 2010, there was a gradual accumulation of publications, with the average annual volume remaining relatively low. However, post-2010, the field experienced a phase of rapid expansion, culminating in a peak in 2022, where the annual publication count exceeded 60, representing a sixfold increase compared to the year 2000. Despite a slight decline following 2022, the overall trend continues to ascend, underscoring the sustained and growing academic interest in this area. Regarding citation trends, the average number of citations for papers published between 2000 and 2010 exhibited a fluctuating upward pattern, likely reflecting the enduring academic influence of seminal studies from that period, such as the establishment of LCNEC pathological diagnostic criteria (17) and updates to the WHO classification system (18). Conversely, the average citation count for papers published post-2010 has shown a downward trend. This may be attributed to factors such as (I) the dilution of impact of individual papers due to the diversification of research topics and (II) the delayed impact of more recent publications. Furthermore, the volume of publications concerning LCNEC has exhibited a declining trend since 2022, potentially attributable to the impact of the COVID-19 pandemic and the concomitant decrease in associated investments.

Figure 2 Annual publication and citation trend analysis.

Country/region distribution

This study identified 45 countries that have produced at least one publication in the domain of LCNEC. The research output from these countries is illustrated in a country map of authors (Figure 3A), where the intensity of color is directly proportional to the number of articles published. The findings indicate that Japan (n=615), the United States (n=513), China (n=486), Italy (n=336), and Germany (n=178) are the primary contributors to the body of literature in this field. Notably, although the United States has a slightly lower number of publications compared to Japan, it exhibits a substantially higher total number of citations (n=6,403) relative to Japan (n=3,301) (Figure 3B). Figure 3C illustrates the temporal trend of research publications in the domain of LCNEC. Japan emerged as an early leader and has consistently maintained a prominent position in this area, followed by the United States, both of which have demonstrated steady growth in research output. Italy’s contribution to the field is also on the rise, albeit at a comparatively slower rate. Although China and Germany entered the field later, since 2010, the volume of Chinese publications has surged dramatically, positioning China as a significant contributor in recent years. In contrast, Germany’s research output has exhibited relatively stagnant growth.

Figure 3 The Global Research Landscape of LCNEC [2000–2024]. (A) Regional distribution of scientific output in different countries related to “LCNEC” from 2000-01 to 2024-12. (B) Ranking of LCNEC related literature citations from 2000-01 to 2024-12. (C) Output over time by country in the LCNEC related fields from 2000-01 to 2024-12. (D) Figure 30. World map of cooperation among countries in the LCNEC-related fields from 2000-01 to 2024-12. LCNEC, large cell neuroendocrine carcinoma.

Utilizing VOSviewer, we have constructed a global map illustrating international cooperation among countries. By setting a minimum threshold of 20 collaborative papers, the analysis is narrowed down to 20 regions. This global cooperation map highlights the extent of inter-country collaboration in this field, with the thickness of the connections being directly proportional to the intensity of cooperation. Currently, China and the United States exhibit the highest frequency of collaboration, followed by European nations, likely due to Europe’s strategic geographical position and the collaborative research mechanisms established under the European Union framework. Emerging partnerships, such as those between Australia and Brazil, are also engaging in LCNEC research, albeit with a lower research output at present. Geographically, LCNEC research is predominantly concentrated in North America, Europe, and East Asia, with comparatively limited participation from Africa and the Middle East (Figure 3D).

Institutional literature analysis

From January 2000 to December 2024, 836 institutions researched LCNEC. Table 1 highlights the top ten, with the National Cancer Center of Japan (n=76), Memorial Sloan Kettering Cancer Center (n=64), and the University of Texas System (n=49) ranking first, second, and third, respectively. Among the ten institutions, three are from the U.S., three from Japan, two from Italy, and one each from Denmark and China. Figure 4 highlights the publication trends of the top five LCNEC research institutions. The National Cancer Center of Japan and Memorial Sloan Kettering Cancer Center are early leaders with consistently high publication outputs. The University of Texas System and UTMD Anderson Cancer Center have stable outputs, with recent growth. The Chinese Academy of Medical Sciences-Peking Union Medical College, a late entrant, has significantly increased its publications since 2019, showing rapid research advancement.

Figure 4 From 2000-01 to 2024-12, the output of research institutions related to “LCNEC” over time. LCNEC, large cell neuroendocrine carcinoma.

Analysis of authors and co-cited authors

Over 4,000 researchers have studied LCNEC. Pelosi G leads with 21 papers, followed by Travis WD with 16, and Papotti M and Yamamoto N with 12 each (Figure 5A). According to Lotka’s Law, most authors publish only a few papers, while a few contribute the majority. The steep decline in the curve shows a high number of authors with just one paper, aligning with Lotka’s pattern of a few prolific contributors dominating LCNEC literature (Figure 5B). In the list of top 10 authors by citation count, Iyoda A, Travis WD and Pelosi G hold the first three positions with 247, 217, and 210 citations, respectively. The author collaboration network (Figure 5C) shows multiple clusters in the LCNEC field, highlighting close collaborations around Pelosi G and Sonzogni A, Yamamoto N, Travis WD, and Dingemans AMC. Connections between clusters are limited, indicating that LCNEC research collaborations often occur within small teams, with a need for more cross-team interaction. Isolated nodes like Chen Y and Zhang J likely represent independent scholars or teams with minimal contact with others in the field.

Figure 5 The academic landscape of LCNEC research. (A) Ranking of authors in LCNEC related fields from 2000-01 to 2024-12. (B) Citation ranking of authors in the LCNEC related fields from 2000-01 to 2024-12. (C). Author collaboration network in LCNEC related fields from 2000-01 to 2024-12. LCNEC, large cell neuroendocrine carcinoma.

Analysis of influential journals and cited journals

The study analyzed 256 journals, with Lung Cancer (n=42, IF =4.5, Q1), Journal of Thoracic Oncology (n=24, IF =21, Q1), and Frontiers of Oncology (n=22, IF=3.5, Q2) having the most publications (Table 2). The top ten cited journals, each with over 400 citations, are shown in Figure 6, with Journal of Clinical Oncology leading at 1,328 citations and an IF of 42.1 (Q1).

Figure 6 Top 10 journals cited by LCNEC from 2000-01 to 2024-12. LCNEC, large cell neuroendocrine carcinoma.

Analysis of references and co-cited documents

This study used reference analysis to assess research progress in LCNEC. Table 3 highlights the ten most-cited articles, with the top one published in 2001 in The European Respiratory Journal. This article, cited 767 times, redefined LCNEC as a high-grade non-small cell lung cancer with neuroendocrine features and marker expression. It established diagnostic standards and suggested the need for more aggressive treatment for LCNEC (17). Two highly cited articles (458 and 426 citations) propose Delta-like ligand 3 (DLL3) as a potential therapeutic target for LCNEC. Since LCNEC and SCLC are neuroendocrine tumors with high DLL3 expression, Rovalpituzumab tesirine (Rova-T), which targets DLL3, was once viewed as a possible treatment for both SCLC and LCNEC (19,20).

Nevertheless, findings from the Phase II TRINITY trial (NCT: 02674568) indicated that Rova-T failed to deliver the anticipated clinical benefits and, conversely, was associated with an elevated incidence of severe toxic reactions (28).

The co-citation network analysis of LCNEC literature reveals two main research clusters (Figure 7). Seminal works, including those by Travis WD [1991] and Asamura H [2006], have traditionally concentrated on topics such as pathological diagnosis and early clinical features (29,30). In contrast, more recent studies, such as those by Rekhtman N [2016] and Fasano M [2015], have shifted focus towards emerging areas, including molecular mechanisms and targeted therapy (31,32). The correlation between these clusters indicates that LCNEC research is evolving, with new directions building on traditional foundations.

Figure 7 Network analysis of co-citation of literature in LCNEC related fields. LCNEC, large cell neuroendocrine carcinoma.

Emerging trends and research priorities based on keyword analysis

A Treemap analysis of literature on LCNEC reveals that “tumors” is the most common keyword (8%), followed by “cancer” (7%) and “chemotherapy” (5%). This indicates a research focus on tumor biology and chemotherapy strategies (Figure 8). Other frequent keywords include “lung” (5%), “large cell neuroendocrine carcinoma” (5%), “classification” (4%), and “survival” (4%), highlighting interest in patient prognosis, tumor classification, and patient survival. Keywords such as “expression” (3%), “lung cancer” (3%), and “carcinoma” (2%) indicate a focus on molecular mechanisms and histological subtypes. Additionally, “diagnosis” (2%), “immunohistochemistry” (2%), and “cisplatin” (2%) highlight the importance of diagnostic biomarkers and chemotherapy regimens in LCNEC-related research.

Figure 8 A tree diagram of the frequency of “LCNEC” related literature from 2000-01 to 2024-05. LCNEC, large cell neuroendocrine carcinoma.

Literature on LCNEC research is categorized into two main dimensions (Figure 9). Dimension 1 (42.05%) spans from basic research, focusing on molecular biology keywords like “gene”, “expression”, and “p53”, to clinical application, with terms like “chemotherapy”, “cisplatin”, and “surgical-management”. Dimension 2 (11.49%) highlights tumor research aspects, with “tumor”, “metastasis”, and “resistance” at one end, and “differentiation”, “prognosis”, and “differential-diagnosis” at the other.

Figure 9 Factor analysis of LCNEC related fields from 2000-01 to 2024-05. LCNEC, large cell neuroendocrine carcinoma.

Trend topics analysis highlights the evolving research focus in this field (Figure 10). From 2000–2010, studies centered on molecular biology techniques like “comparative genomic hybridization” and “overexpression”, and tumor types such as “bronchial carcinoids”. Over time, core topics like “lung”, “gene”, “neoplasms”, “adenocarcinoma”, and “expression” gained prominence. Recently (2016–present), there has been a shift towards clinically relevant topics like “tumors”, “lung cancer”, “classification”, “diagnosis”, “features”, “chemotherapy”, and “cisplatin”, reflecting a focus on clinical application in LCNEC research. The rise of targeted therapy studies, such as “ALK-rearrangement”, suggests a move towards precision treatment strategies.

Figure 10 Trends in research topics related to LCNEC from 2000-01 to 2024-05. LCNEC, large cell neuroendocrine carcinoma.

Discussion

This study is the inaugural bibliometric analysis of LCNEC, encompassing 694 articles from the WoSCC between 2000 and 2024, to systematically summarize research topics, trends, literature sources, and global impact.

LCNEC represents a rare and highly malignant subtype of lung cancer, characterized by a poor prognosis and presenting substantial clinical challenges on a global scale (33). Our research indicates a consistent increase in the volume of literature pertaining to LCNEC, reflecting heightened scholarly interest in this disease in recent years. Notably, the surge in LCNEC-related publications post-2015 can be attributed to several factors. Firstly, advancements in immunohistochemistry, coupled with the 2015 revision of the World Health Organization’s lung tumor classification, have enhanced diagnostic accuracy and standardized pathological assessments for LCNEC (34). Secondly, the aggressive nature of LCNEC, its unfavorable prognosis, and the absence of standardized treatment protocols have spurred researchers to investigate more precise therapeutic strategies. Retrospective studies and case series analyses further underscore the clinical heterogeneity and therapeutic controversies associated with this malignancy (33). Moreover, genomic research has delineated molecular subtypes within LCNEC that resemble either SCLC or NSCLC, thereby providing a theoretical basis for the development of targeted therapies and immunotherapeutic approaches. The identification of novel targets, such as DLL3, has significantly advanced the field of translational medicine (35-38). Concurrently, the development of organoid models has effectively addressed the previous deficiency in preclinical models, while multicenter collaborations have improved data integration capabilities for rare cases (39). Furthermore, there has been a growing academic interest in neuroendocrine tumors, particularly LCNEC, which exhibits characteristics of both SCLC and NSCLC, making it a prominent topic of research (40). Collectively, these factors have propelled the rapid advancement of LCNEC research since 2015. Consequently, it is anticipated that this field will continue to expand in the forthcoming years.

The research findings indicate that Japan, the United States, China, Italy, and Germany are the leading countries in terms of the number of publications in the field of LCNEC, as illustrated in Figure 3. Notably, China and the United States exhibit the highest frequency of collaborative efforts, with European countries following. This trend may be attributed to their accelerated economic development and enhanced investment in research funding within pertinent domains, which have collectively facilitated an increase in scholarly output related to LCNEC. Collaboration with developed countries boosts scientific productivity due to their advanced medical standards and rich research resources. To promote balanced global LCNEC research, developed countries should strengthen ties with more regions, especially underdeveloped areas like Africa and the Middle East. The U.S. dominates with five of the top ten journals, while China, despite being third in publication volume, has only one, indicating a need to improve journal quality and international influence. Key future directions for LCNEC research include enhancing international cooperation, improving research quality, and increasing journal impact.

An examination of academic influence reveals that Japan’s National Cancer Research Center and North America’s Memorial Sloan-Kettering Cancer Center possess substantial research accumulation in the domain of LCNEC. Notably, the Chinese Academy of Medical Sciences and Peking Union Medical College have exhibited a marked upward trajectory on the international academic landscape of this field, attributable to their high-quality research output in recent years. An analysis of journal influence indicates that the Journal of Clinical Oncology stands as the most influential core journal in this domain, evidenced by its impressive impact factor (IF =50.717) and its contribution to 21.4% of the cumulative citations of LCNEC-related studies within the analyzed literature. Regarding authorship, Pelosi G, Travis WD, Papotti M, and Yamamoto N have made notable contributions to the field of LCNEC. The seminal document, “The New World Health Organization Classification of Lung Tumours”, has systematically redefined the pathological diagnostic framework for large cell neuroendocrine carcinoma LCNEC. It has established the use of immunohistochemical markers—CD56, Synaptophysin, and Chromogranin A—as the clinical gold standard (24). Subsequent highly cited studies [doi: 10.1126/scitranslmed.aac9459 and doi: 10.1016/s1470-2045(16)30565-4] have validated the potential of DLL3 as a targeted therapeutic approach for LCNEC (19,20).

Our team employed Treemap analysis, factor analysis, and Trend Topics analysis to elucidate the focal points, thematic distribution, and dynamic evolution of research in the field of LCNEC. The primary focus within the LCNEC research domain encompasses biological characteristics, therapeutic strategies, and molecular classification, among other areas. In the 2021 World Health Organization classification, LCNEC is categorized as a high-grade neuroendocrine carcinoma of the lung and is associated with SCLC (41). Histologically, LCNEC demonstrates neuroendocrine differentiation (41); however, its cellular morphology more closely resembles that of NSCLC (42). In contrast, its clinical behavior and therapeutic response align more closely with those of SCLC (43,44). Rekhtman et al. employed second-generation sequencing to elucidate the molecular heterogeneity of LCNEC, identifying two distinct subtypes: small-cell-like LCNEC (SCLC-like LCNEC) and non-small-cell-like LCNEC (NSCLC-like LCNEC). The SCLC-like LCNEC subtype is characterized by deletions in the RB1 and TP53 genes, whereas the NSCLC-like LCNEC subtype is associated with mutations in the KRAS gene, alterations in the STK11/KEAP1 genes, and/or mutations in the TP53 gene (31). Furthermore, the research conducted by Hermans et al. identified instances where LCNEC coexists with adenocarcinoma, thereby further illustrating the significant heterogeneity of LCNEC (42,45).

Currently, there is no established consensus regarding the treatment strategies for LCNEC. In clinical practice, chemotherapy regimens are primarily adapted from those used for SCLC or NSCLC (35,46,47). For patients with early-stage LCNEC who are eligible for surgical intervention, postoperative adjuvant chemotherapy may enhance disease-free survival (48); however, this approach lacks robust support from prospective study data. In cases of advanced LCNEC, first-line treatment predominantly involves platinum-based combination chemotherapy, although the response rate remains suboptimal (49).

Furthermore, LCNEC exhibits a propensity for developing resistance to conventional chemotherapy (45). Consequently, innovative therapeutic approaches, including PD-1/PD-L1 inhibitors and targeted therapies, are currently under investigation. DLL3 is markedly expressed in LCNEC, and the therapeutic potential of bispecific antibodies targeting DLL3, such as obrixtamig, is being assessed in clinical trials (50,51). Due to the molecular heterogeneity of LCNEC, certain cases harbor driver gene mutations associated with NSCLC, such as EGFR and ALK mutations; however, the efficacy of targeted therapies in these instances is limited (43,45). Additionally, preliminary data suggest that some patients who do not respond to first-line treatment may benefit from subsequent immunotherapy (52,53). Nevertheless, further prospective studies are essential to establish standardized treatment protocols for LCNEC.

LCNEC is an infrequent and highly aggressive high-grade neuroendocrine tumor, characterized by a paucity of reliable preclinical models due to the limited availability of clinical specimens. The rarity and aggressive nature of LCNEC contribute to the scarcity of clinical samples, which in turn hampers the development of dependable experimental models. The successful establishment of organoid models has emerged as a significant platform for investigating the biological characteristics and mechanisms of drug resistance in LCNEC. LCNEC-associated tumoroids present a valuable model for directly assessing the efficacy of therapeutic agents. Drug susceptibility assays have indicated that CDK4/6 inhibitors may be effective for treating non-small cell large cell neuroendocrine carcinoma, whereas Aurora A kinase inhibitors may be more appropriate for small cell large cell neuroendocrine carcinoma or subtypes exhibiting MYC amplification (35). These findings provide a foundational experimental basis for informing clinical treatment strategies. Furthermore, organoids are instrumental in advancing our understanding of the molecular pathogenesis of LCNEC (42). Nonetheless, despite the promise of organoid technology in the context of LCNEC, several challenges remain, including a low success rate in culture—attributable in part to tumor heterogeneity—and a lack of standardized protocols. Future efforts should focus on optimizing culture conditions to enhance the utility of this technology (54-56).

This study is subject to certain limitations. Firstly, the data sources are confined to the WoSCC database, which may result in incomplete literature searches and the exclusion of pertinent studies available in other databases. Secondly, the inclusion criterion was restricted to English-language publications, potentially introducing language bias and not fully capturing the entirety of research findings in the field of LCNEC. Despite these limitations, we contend that this study offers a substantial contribution to the understanding of the topic.

Conclusions

Research on LCNEC has transitioned from a focus on pathological characterization to an emphasis on molecular typing and precision therapy. Nonetheless, significant challenges persist, including the uncertainty surrounding optimal treatment strategies, the emergence of treatment resistance, and the scarcity of prospective clinical trials. Future advancements in this domain should be facilitated through the integration of multi-omics approaches and international multi-center collaborations. Additionally, there is a strong anticipation for increased global partnerships and the initiation of prospective clinical trials.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the BIBLIO reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-727/rc

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-727/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-727/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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